Pembrolizumab/chemotherapy may prolong survival in classical Hodgkin lymphoma

Pembrolizumab (Keytruda) appeared to prolong survival in combination with conventional ifosfamide, carboplatin, and etoposide (ICE) chemotherapy in patients with relapsed/refractory Hodgkin lymphoma scheduled to undergo autologous hematopoietic stem cell transplantation (AHSCT) , according to data from a non-randomized phase 2 trial published in a clinical trial (NCT03077828) JAMA Oncology.

“The addition of checkpoint inhibitors could significantly increase the number of patients with relapsed or refractory disease eligible for AHSCT and significantly increase the overall success rate of salvage therapy,” said the study. the author says.

The overall response rate (ORR) in 37 evaluable patients was 97.3% (95% CI, 85.8%-99.9%), with 10.8% (95% CI, 3.0%-25.4%) having a partial response (PR ), with a complete response (CR) of 86.5% (95% CI, 71.2%–95.5%). The 2-year estimated progression-free survival (PFS) was 87.2% (95% CI, 77.3%-98.3%). The corresponding figure for overall survival (OS) was 95.1% (95% CI, 88.8%-100%). These survival outcomes met the primary endpoint above estimated historical outcomes with second-line chemotherapy regimens.

Responses were assessed using 18F-fluorodeoxyglucose-positron emission tomography and computed tomography (FDG-PET/CT) imaging. The investigators also biopsied two of her FDG-PET-positive new areas, revealing a noncaseating granuloma in one and a reactive lymph node in the other of hers.

“Multiple studies have demonstrated that second-line CR achievement with FDG-PET/CT is a strong predictor of AHSCT outcome,” the researchers wrote. “Therefore, improving CR rates to salvage regimens is a top priority that is expected to lead to better clinical outcomes, including OS…. Or it could significantly increase the number of patients with refractory disease and the overall success rate of salvage therapy.”

Investigators in this single-arm, non-randomized Phase 2 trial enrolled 37 patients from five centers during the cumulative period from April 20, 2017 to October 29, 2020. 43% of him in this population had primary refractory disease and 32% had recurrent disease. Within 1 year after completing frontline therapy. Additionally, 16% had colossal disease at enrollment. The frontline therapy used in his 92% of patients was a combination of doxorubicin, bleomycin, vinblastine, and dacarbazine. More patients had stage I/II disease (46%) than stage III/IV disease (38%) at baseline.

The median age was 34 years (range, 19–70 years). Most patients were female (68%) and Caucasian (70%), others were African American (16%) or Asian (3%).

Patients received 200 mg pembrolizumab intravenously on day 1 of each of two cycles. They also treated standard ICE salvage chemotherapy with ifosfamide at a dose of 5 g/m on day 2 in combination with an equivalent dose of Mesnex by continuous intravenous infusion over 24 hours, with an area under the curve of 2 days. The eyes received etoposide from 5 to a maximum of 800 mg intravenously on days 1 to 3 at a dose of 100 mg/m2 per day. A treatment cycle he started every 21 days. After the second cycle, stem cell mobilization and collection was completed, after which the patient received her one cycle of pembrolizumab monotherapy.

The primary endpoint of this trial was the CR rate. Secondary endpoints included PFS, OS, stem cell mobilization and adverse effects (AEs).

A total of 42 patients received at least one dose of pembrolizumab and were included in the safety analysis. Overall, 81% experienced an AE that investigators attributed to treatment. Grade 3/4 AEs occurred in 22 of her patients, including 15 with thrombocytopenia, 11 with anemia, 9 with neutropenia, 10 with lymphopenia, 12 with I had leukopenia.

Six serious adverse events considered potentially related to pembrolizumab occurred in five patients. One of her patients with severe coronary artery disease experienced ventricular fibrillation during stem cell harvest. Another patient experienced acute respiratory failure during recovery of white blood cell counts after AHSCT. Apart from this instance, no serious pembrolizumab-related autoimmune events delayed protocol treatment. All serious AEs were grade 1/2.

“Concomitant administration of pembrolizumab with conventional ICE chemotherapy is a well-tolerated and effective treatment strategy for patients with relapsed or refractory classical Hodgkin lymphoma, resulting in high CR rates and We found that the patient proceeded to AHSCT,” the investigators concluded. “In the presence of checkpoint inhibitors, pseudoprogression, flare reactions, granulomatous and reactive processes may obscure the true rate of complete metabolic response, and results should be directly compared to conventional regimens.” becomes difficult.”

To validate these findings, the researchers are conducting a larger, randomized phase 3 trial comparing standard chemotherapy alone with regimens including checkpoint inhibitors such as pembrolizumab in this disease area. suggested that a


Brian LJ, Kaslo C, Allen PB, et al. Pembrolizumab added to ifosfamide, carboplatin, and etoposide chemotherapy for relapsed or refractory classical Hodgkin lymphoma: a multicenter phase 2 investigator-led nonrandomized clinical trial. JAMA on callPublished online March 16, 2023. doi:10.1001/jamaoncol.2022.7975

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